The ETS family of transcription factors have been shown to be associated cell proliferation and a variety on neoplastic transforming events, especially those involving the erythroid lineage. We have been interested in the role of the ETS-1 and FLI-1 genes, two members of the ETS family of transcription factors, in hematopoeitic neoplasia and normal differentiation. Members of the ETS family have been shown to be involved in aspects of both erythroid and megakaryocytic differentiation in vivo. Our previous work had indicated that FLI-1 acted positively in certain pluripotent human hematopoeitic cell lines to activate genes normally expressed during megakaryocytic differentiaton, while blocking expression of genes associated with erythroid differentiation. We have extended our studies of the mechanisms by which MKK/MAPK and FLI-1 both can activate the expression of megakaryocytic markers in K562 and HEL cells. Our data indicate that these effects may involve two separate pathways, and that the presence of exogenous FLI-1 alters the effects of MKK/MAPK activation and inhibition. In addition these studies suggest that the regulation of the gpII<sub>B</sub> and gpIII<sub>A</sub> protein levels may be differentially affected by these pathways. - erythroid, ETS1, FLI1, HEL, hematopoiesis, K, 2, megakaryocyte, transcription factor, - Neither Human Subjects nor Human Tissues